This investigation proposes to study the teratogenic effect of Sodium Valproate (VA) on the craniofacial growth and development in the A/J mouse fetus. A drug dosage resulting in drug serum levels within the therapeutic (human) range, producing the greatest number of craniofacial abnormalities without being embryolethal and/or toxic to the dams will be utilized in the following experiment. On day seven of gestation, osmotic minipumps containing the drug or distilled water for controls will be implanted subcutaneously in each of the dams. The implanted minipumps will provide continuous administration of VA for seven consecutive days. Drug serum levels will be determined daily. Following implantation of the minipumps, pregnant dams will be placed in their respective sealed environmental chambers until the 14th day of gestation. Six experimental groups of 10 animals each will receive VA under normoxic, hyperoxic or hypoxic conditions. On day 18 all pregnant dams will be sacrificed by cervical dislocation. Two-thirds of the live fetuses will be examined using Wilson's technique. The remaining one-third will be processed for detection of skeletal defects. Craniofacial skeletal measurements will be recorded and compared among the three experimental groups. The principal objectives of the proposed study are: 1) to assess the teratogenicity of VA on the craniofacial development and growth of the A/J mouse fetus, and 2) to determine whether the expected teratogenic effects in the drug treated A/J mouse fetus can be ameliorated by increasing the maternal oxygen environment during pregnancy, and 3) to assess the feasibility of an implanted osmotic minipump in teratogenic studies. Although one cannot extrapolate directly from rodent experiments to the human condition, the rodent model may serve as a possible indicator of the teratogenicity of the experimental drug, and/or the protective effect of hyperoxia on the fetal animal. Other animal species, especially the primates, should be examined under these conditions before any clinical significance is attached to the human.